tbuckley/cabot-search huggingface dataset:
Integration of geriatric assessment in cancer care for senior adults during COVID-19 pandemic.
Authors: Mohammed Al-Jumayli, Cassandra Vonnes, Marina Sehovic, Martine Extermann
Journal: Journal of Clinical Oncology (2022)

e24027 Background: Older patients with cancer are particularly vulnerable, and the risk of mortality and morbidity during this pandemic is high. Comprehensive geriatric assessment (CGA) helps in predicating toxicity and improve outcomes. SAOP3 is validated geriatric screening tool that can efficiently identify deficits in different GA domains. It was developed to determine when a multidisciplinary team consultation with GA-intervention is required. Methods: We performed a retrospective review of institutional cancer registry. We compared 2 groups of cancer patients ≥ 70 years old who completed SAOP3 questionnaire in the pre-COVID (9/1/2019- 3/10/2020) and during the pandemic period (3/11/2020-12/31/2020). Fisher’s exact test was used to statistical analysis. Analytical models were adjusted for age, cancer histology, stage, therapy type, and GA variables. Results: 951 patients were included (499 prepandemic,452 during pandemic). Median age was 76.6 yrs. (range = 71-86). A 50.7% male, 48.3% female and 34% (323) have metastatic disease. The capture and completion rate of SAOP3 were 82% (779) and 86% (817) respectively. There was a significant psychosocial impairment during the pandemic. More patients were feeling depressed 26% (118) during Vs. 3% (15) prior pandemic (P &lt; 0.001). The caregiver availability was different with 47% (212) during pandemic compared to 52% (259) in pre-pandemic (P = 0.0013). There was a statistically significant difference in the fall history with 4% (20) in pre-, in contrast to 10% (45) during pandemic (P = 0.003). There was a numerical difference in the cognitive impairment during the pandemic in compared to the pre-COVID [34% (171), 52% (235) respectively], but it was not statistically significant (P = 0.154). There was no difference observed in nutritional domains between the two groups. Conclusions: Data regarding patients’ domains of a CGA are crucial for optimal care. Screening with the SAOP3 questionnaire captured significant changes in CGA domains associated with the pandemic. These findings also suggest that Integration of high-yield brief geriatric screening tools such as SAOP3 is feasible in busy practice during the pandemic. It can help identify specific impairment of older cancer patients and trigger appropriate interventions to improve the quality of life and clinical outcomes.
Desmoplastic small round cell tumor: Analysis of surveillance, epidemiology, and end results (SEER) database 1975 to 2018.
Authors: Syed Hamza Bin Waqar, Hassam Ali, Taha Sheikh, Danae M. Hamouda
Journal: Journal of Clinical Oncology (2022)

e23540 Background: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma with a poor prognosis. The incidence and prognosis of patients with DSRCT have been inadequately understood. Survival analysis for DSRCT has been sparsely investigated in a population-based study. Methods: We conducted a retrospective cohort study using the SEER 9 Registry (1975-2018). Site recode International Classification of Diseases for Oncology (ICD-O-3) 8806/3 was used via SEER*Stat software to select DSRCT cases. SEER*Stat software estimated annual percent changes, and Poisson regression estimated risk ratios. Cox regression models were constructed to estimate the hazard ratio for survival at five years. The period-specific rates were portrayed as rate per 1,000,000. Results: The male and female age adjusted DSRCT incidence rates were 0.22 and 0.05, respectively (p &lt; 0.05). Incidence rate of DSRCT has been rising in the last two decades from 1975–2000 to 2001-2018 (0.013 vs. 0.31,p &lt; 0.05). Males have a higher age adjusted DSRCT incidence rate (0.22 vs. 0.05,p &lt; 0.05), and non-metropolitan counties had a higher incidence rate than metro counties (1.14 vs. 0.14,p &lt; 0.05). The observed survival at 12, 36, and 60 months was 81%, 39.9%, and 23.4%, respectively. There was no significant difference in survival between females and males. Ages greater than 70 years had poor survival compared to ages less than 60 years (p &lt; 0.001). Compared to surgery with chemotherapy, surgery combined with radiotherapy and chemotherapy was associated with a 62% lower risk of mortality (p&lt; 0.001). Conclusions: This study reveals that DSRCT incidence has been increasing since 2000, is more common in white males. Gender may not affect survival in DSRCT, and surgery combined with chemoradiotherapy is associated with improved survival outcomes compared to surgical management with chemotherapy alone. Further comparative data would be beneficial to confirm reported findings.[Table: see text]
Subcutaneous (SC) isatuximab administration by an on-body delivery system (OBDS) in combination with pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM): Interim phase 1b study results.
Authors: Hang Quach, Gurdeep Parmar, Enrique Ocio, H. Miles Prince, Albert Oriol Rocafiguera, Nobuhiro Tsukada, Kazutaka Sunami, Pierre Bories, Chatchada Karanes, Sumit Madan, Dorothee Semiond, Marlene Inchauspe, Sandrine Macé, Petra B. Musholt, Florence Suzan, Philippe Moreau
Journal: Journal of Clinical Oncology (2022)

8025 Background: Intravenous (IV) isatuximab (Isa) + Pd is approved for the treatment of RRMM patients (pts). SC delivery would optimize convenience of administration. Prior results showed that SC Isa administered by syringe pump has efficacy and safety profiles comparable to IV Isa; the recommended Phase 2 dose (RP2D) was 1400 mg (IMW21 P-207). Methods: This multicenter Phase 1b study evaluated safety, PK and efficacy of SC vs IV Isa + Pd in RRMM pts after ≥2 prior treatment lines. Pts were randomized 2:1 to SC1000 mg or IV 10 mg/kg and to SC1400 mg or IV. An expansion cohort was later implemented with SC Isa administered at the RP2D via OBDS, a wearable bolus injector applied to the abdomen by a healthcare professional. Primary endpoints (EPs) were safety, including injection site reactions (ISRs), and PK. Main secondary EPs were overall response rate (ORR) and progression-free survival (PFS). Results: 56 pts were randomized and treated: 12 Isa IV, 12 Isa SC1000, 10 Isa SC1400 and 22 OBDS pts. At study entry, ISS stage II–III was 67% in IV, 33% in SC1000, 60% in SC1400 and 50% in OBDS pts. On Jan 20, 2022, 33% IV, 25% SC1000, 50% SC1400 and 86% OBDS pts remained on treatment. Due to sequential accrual, median follow-up (FU) was longer in IV (20.6 mo) and SC1000 (23.8 mo) than SC1400 (18.1 mo) and OBDS (6.5 mo) pts. Infusion reactions (IRs) were infrequent (≤10% in each cohort, all Grade [G] 2), only at first IV or SC infusion/injection, with no IRs in OBDS. Local tolerability of OBDS was very good, with 5 (22.7%) pts experiencing 7 ISR episodes, all G1, out of 305 administrations (2.3%): 5 injection site erythemas, 1 injection site hemorrhage, and 1 injection site induration. Median duration of OBDS injection was 10 min. Incidence of G4 neutropenia was lower in SC1000 (42%) vs the other cohorts (55–60%). The lower % of ≥G3 treatment-related AEs in OBDS (77%) vs the other cohorts (≥80%) may be due to shorter FU. Best overall responses are shown in table; longer FU is needed for OBDS pts. Median PFS was 22 mo in IV, 12.5 mo in SC1000 and not reached in SC1400 and OBDS pts. PK and CD38 receptor occupancy results in OBDS pts are consistent with those observed in SC1400 with pump. Conclusions: SC Isa administered by OBDS shows a safety profile consistent with IV administration with no IRs and excellent local tolerability. Efficacy in the SC cohorts was comparable to the Phase 3 ICARIA results. Isa SC administration by OBDS is well tolerated, requires a short duration of injection and provides a convenient hands-free option. Clinical trial information: NCT04045795. [Table: see text]
IV vitamin C with chemotherapy for cisplatin ineligible bladder cancer patients (CI-MIBC) first-stage analysis NCT04046094.
Authors: Rahul Atul Parikh, John A. Taylor, Qi Chen, Benjamin L. Woolbright, Ping Chen, Elizabeth Marie Wulff-Burchfield, Jeffrey Holzbeierlein, Roy A. Jensen, Jeanne A. Drisko
Journal: Journal of Clinical Oncology (2022)

e16540 Background: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ̃40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usually proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy in other models. This single-arm, Simon 2-stage, window of opportunity trial included IVC with single cycle GCa to evaluate pathologic downstaging. We report on the interim first stage analysis of 12 patients. Methods: Patients with newly diagnosed CI-MIBC were enrolled and received single cycle GCa and IVC titrated to peak plasma concentration of 350 to 400 mg/dL (̃20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. The primary outcome is pathological stage at cystectomy. Patients are then followed per NCCN guidelines with standard of care bloodwork, physical exam and imaging studies until progression and/or death. QOL is being evaluated by Functional Assessment of Cancer Therapy-Bladder (FACT-Bl). Results: All 12 patients completed GCa/IVC with 11 having had a cystectomy and 1 pending surgery. Pathological downstaging (yp &lt; T2) was noted in 4 patients with 3 CRs (ypT0N0Mx) and 1 with residual ypTisN0Mx only. Of note, 1 CR was seen in a patient with locally advanced plasmacytoid variant. Participants tolerated treatment well with minimal treatment related AE/SAEs. Conclusions: Interim analysis of GCa-IVC NAC shows good tolerability with &gt; 36% rate of downstaging. Of those with a pathological response, 75% achieved a CR. Continuation criteria has been met for stage 2. FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion. Clinical trial information: NCT04046094.
PERCEPTION: Phase II investigational study of pembrolizumab combination with chemotherapy in platinum-sensitive recurrent low-grade serous ovarian cancer— A NOGGO trial.
Authors: Jacek P. Grabowski, Lea-Jean Pietzke, Dario Zocholl, Philipp Harter, Florian Heitz, Radoslav Chekerov, Jalid Sehouli
Journal: Journal of Clinical Oncology (2022)

TPS5613 Background: Low-grade serous ovarian cancer (LGSOC) represents a minority within the group of invasive epithelial ovarian malignancies. Recent analyses showed a very limited responsiveness to chemotherapy in LGSOC. Since bevacizumab many years ago, none other agents have been approved in LGSOC. There is a high demand of new therapy combinations with modern substances to improve the response rate and prognosis in this group of patients. Immune check-point inhibitors provide a new possibility which showed to be effective in different malignant diseases as well as in selected ovarian cancer patients. In this study, the standard chemotherapy is going to be combined with pembrolizumab in recurrent LGSOC cases with therapy free interval (TFI) over 6 months after last platinum-based chemotherapy. To the authors knowledge no comparable studies have been performed or planned. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Methods: PERCEPTION/NOGGO-ov44 (NCT04575961) clinical trial is a multi-center, single-arm phase 2 study to evaluate pembrolizumab therapy concomitant to platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin, carboplatin plus gemcitabine or carboplatin monotherapy) and as maintenance in recurrent low-grade serous ovarian cancer cases. LGSOC patients with progression or recurrence at least six months after most previous platinum-containing therapy and in good general performance (ECOG 0 or 1) are eligible to participate in this clinical trial. The primary objective is the 12 months progression free survival (PFS) rate. Secondary end-points include overall survival, response rate (RR), PFS and RR according to Ki67 expression levels, time to first subsequent therapy (TFST) and its response, safety and quality of life. The trial is planned according to Simon’s two-stage design with total sample size up to 33 patients. The null hypothesis is PFS-rate after 12 months of 20%. In the first phase 18 patients will be enrolled and if at least 5 patients show PFS after 12 months the study is going to be continued with an additional 15 patients. The trial is claimed successful, if at least 11 patients show PFS after 12 months. Assuming a true PFS-rate of 40%, this trial has 5% type I error rate and 80% power. Clinical trial information: NCT04575961.
Association of antibiotic therapy and treatment efficacy in patients with renal cell carcinoma receiving immune checkpoint inhibitors.
Authors: Avery Braun, Mengying Deng, Elizabeth A. Handorf, Philip Abbosh
Journal: Journal of Clinical Oncology (2022)

4556 Background: There is growing evidence indicating that gut microbiome content is associated with the effectiveness of immune checkpoint inhibitory (ICI) therapy in various cancer types. Antibiotic therapy (ABT) induces significant changes in gut microbiota; however, the effects of ABT on oncologic outcomes with ICI therapy has only been explored in small, single-institution studies. We aimed to investigate the relationship between ABT on overall survival (OS) and real-world progression free survival (rwPFS) in subjects with advanced renal cell carcinoma (RCC) treated with ICI utilizing a national database. Methods: We queried the nationwide electronic health record (EHR)-derived de-identified FlatIron Health (FIH) database after Institutional Review Board approval was obtained and included a waiver of informed consent to select 1809 subjects who received ICI therapy. Patient characteristics were described and compared between those with known ABT use and without known ABT use (in the 3 months pre/post ICI initiation) using ANOVA and Chi-square tests. rwPFS and OS were calculated from date of initiation of ICI to date of real-world progression/date of death. Three-month landmark Kaplan Meier and log-rank tests were used to compare rwPFS and OS between groups defined by ABT use (any ABT, and ABT in 3 months pre-ICI vs 3 months post-ICI initiation). Cox proportional models were used to investigate the association between rwPFS, OS, and antibiotic use, adjusting for patient characteristics. Results: Patients receiving ABT group were younger (p = 0.007) and more likely female (p = 0.024) but similar in other measured demographic variables. rwPFS (median: 9.03 vs 11.6 months; p = 0.015) and OS (median: 23.7 vs 31.8 months; p = 0.019) were significantly shorter in the with-ABT group than in the without-ABT group. When assessing ABT use 3 months prior to initiation of ICI (vs ABT during/no known ABT use), neither rwPFS (median: 9.53 vs 11.66, p = 0.38) nor OS (median: 23.7 vs 22.6 months; p = 0.38) were significantly different. However, rwPFS (median: 23.5 vs 14.0 months vs not reached; p = 0.004) and OS (median: 36.2 vs 22.5 vs 31.8; p = 0.007) were statistically significantly different when stratifying based on exposure and timing of ABT amongst pre-ICI initiation ABT, post-ICI initiation ABT and no ABT groups, respectively. Multivariable analysis identified as a significant predictor of rwPFS (HR = 0.725, CI = 0.579-0.908; p =.005) and OS (HR = 0.722, CI = 0.573-0.911; p = 0.006). Conclusions: This study identifies a significant negative prognostic association of ABT administration on survival in advanced RCC treated by ICI in the first line setting. These results are consistent with the growing body of evidence suggesting that alterations in gut microbiome secondary to antibiotics appear to blunt efficacy of ICI treatment and emphasize the importance of antibiotic stewardship.
Consensus molecular subtypes (CMS) as prognostic and predictive biomarkers of panitumumab (Pmab), fluorouracil and folinic acid (FU/FA) or FU/FA maintenance therapy following Pmab-FOLFOX induction in <i>RAS</i> wildtype metastatic colorectal cancer (mCRC): PANAMA trial (AIO-KRK-0212).
Authors: Beeke Hoppe, Dominik Paul Modest, Luisa Keilholz, Il-Kang Na, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Ludwig Fischer Von Weikersthal, Eray Goekkurt, Anke C. Reinacher-Schick, Stefan Kasper, Andreas Jay Kind, Annika Kurreck, Swantje Held, Volker Heinemann, David Horst, Armin Jarosch, Sebastian Stintzing, Tanja Trarbach, Arndt Stahler
Journal: Journal of Clinical Oncology (2022)

3537 Background: Consensus molecular subtypes (CMS1-4) of colorectal cancer were evaluated as prognostic and predictive biomarkers in the PANAMA trial. PANAMA compared maintenance therapy with panitumumab (Pmab) and fluorouracil/folinic acid (FU/FA) vs. FU/FA alone after Pmab-FOLFOX induction therapy in RAS wildtype mCRC. Methods: Gene expression was measured after mRNA isolation in 179 of 248 patients of the full analysis set. The analysis was conducted using a customized Nanostring PanCancer Progression Panel. The original CMS classifier was re-derived for Nanostring data using a multinomial regression analysis.Median progression-free (PFS) and overall survival (OS) since start of maintenance were estimated by Kaplan-Meier-method and Cox-regression, using the log rank test. Objective response rates (ORR) of maintenance therapy were compared by Chi-square-test. Results: Prevalence of CMS was: CMS1, n = 15 (8.4 %); CMS2, n = 82 (45.8 %); CMS3, n = 20 (11.2 %) and CMS4, n = 62 (34.6 %). A prognostic impact of CMS regardless of treatment was not evident for PFS (p = 0.245) and OS (p = 0.169), but for ORR (p = 0.022), with CMS1 and CMS3 being associated with unfavourable efficacy during maintenance therapy. Potential predictive effects of CMS were observed in patients with CMS2 and CMS4 tumours. In CMS2 and CMS4 tumours, ORR was significantly higher when treated with Pmab-FU/FA in maintenance therapy (CMS2: 56.5% vs 30.6%, p = 0.026; CMS4: 55.6% vs. 28.6%, p = 0.040). In patients with CMS2 mCRC, this translated into a significant effect on PFS (Hazard ratio: 0.61 (95% CI 0.38 – 0.99) p = 0.046 (Table). Conclusions: CMS have limited prognostic impact for pmab-based maintenance therapy. However, CMS2 and CMS4 are positively associated with Pmab efficacy during maintenance therapy in the PANAMA trial. Further trials are necessary to confirm these results. [Table: see text]
Prognostic value of the lung immune prognostic index in patients with untreated advanced renal cell carcinoma (aRCC) receiving nivolumab plus ipilimumab (N+I) or sunitinib (SUN) in the CheckMate 214 trial.
Authors: Lucia Carril-Ajuria, Robert J. Motzer, Nizar M. Tannir, David F. McDermott, Hans J. Hammers, Elizabeth R. Plimack, Frede Donskov, Brian I. Rini, Ruiyun Jiang, Chung-Wei Lee, Heshani Desilva, Laurence Albiges
Journal: Journal of Clinical Oncology (2022)

4538 Background: The Lung Immune Prognostic Index (LIPI), defined by lactate dehydrogenase (LDH) and derived neutrophil to lymphocyte ratio (dNLR), has been shown to correlate with outcomes of immune checkpoint inhibitor therapy in patients (pts) with lung and other cancers, including pts with previously treated aRCC receiving nivolumab in the phase 2 NIVOREN GETUG-AFU 26 trial. We report an analysis of LIPI in pts with previously untreated aRCC receiving N+I or SUN in the randomized phase 3 CheckMate 214 trial with 5 years minimum follow-up. Methods: Data were used from CheckMate 214 comparing N+I (N 3 mg/kg + I 1 mg/kg) vs SUN (50 mg) for untreated aRCC (N = 1096). Pts with available LIPI data were categorized into 3 LIPI groups (good [LG], dNLR ≤ 3 and LDH ≤ upper limit of normal [ULN]); intermediate [LI], dNLR &gt; 3 or LDH &gt; ULN; and poor [LP], dNLR &gt; 3 and LDH &gt; ULN). This analysis focused on the prognostic value of LIPI using overall survival (OS) outcomes. Univariable analyses (UVAs) were conducted to evaluate LIPI groups alongside known risk factors including age, sex, IMDC risk, baseline PD-L1 status, prior nephrectomy, and baseline tumor burden. Variables that were statistically significant in UVAs ( P &lt; 0.1) were included in the full multivariable analyses (MVAs), from which a reduced model was generated. Results: A total of 1085 pts were evaluable for LIPI (N+I, n = 542; SUN, n = 543). Pts were distributed evenly between treatment arms for all 3 LIPI groups, but distribution between LIPI groups was unbalanced, with most pts grouped as LG (Table). OS outcomes were improved with N+I over SUN across all LIPI groups. Moreover, pts in the LG group had better OS outcomes vs pts in the LI or LP groups regardless of treatment, but with more distinct differences between LIPI groups in the SUN arm (Table). Final MVA results showed the LIPI correlated with OS for LI vs LG in the N+I arm and for LI vs LG and LP vs LG in the SUN arm (Table). Conclusions: These results from CheckMate 214 indicate the potential prognostic value of the LIPI in pts with untreated aRCC receiving N+I or SUN. Additional analyses are ongoing to further investigate the prognostic value of LIPI in this pt population and its impact on other clinical outcomes. Clinical trial information: NCT02231749. [Table: see text]